Zhou and Agrawal et al, Bioorganic & Medicinal Chemistry Letters 8 (1998) 3269-3274, reports on 2′-O methylribonucleoside gapmer phosphorothioate oligonucleotides, which have flanks which each comprise four and five 2′-O methylribonucleoside units, where each flank comprises two phosphodiester bonds. The introduction of phosphodiester bonds was found to result in intravenous distribution patterns similar to the fully phosphorothioate molecules, but have reduced side effects.